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Empagliflozin, a sodium-glucose co-transporter (SGLT) inhibitor, reduces heart failure and sudden cardiac death but the underlying mechanisms remain elusive. In cardiomyocytes, SGLT1 and SGLT2 expression is upregulated in diabetes mellitus, heart failure, and myocardial infarction. We hypothesise that empagliflozin exerts direct effects on cardiomyocytes that attenuate diabetic cardiomyopathy. To test this hypothesis, cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) were used to test the potential effects of empagliflozin on neutralization of cardiac dysfunction induced by diabetic-like cultures. Our results indicated that insulin-free high glucose culture significantly increased the size of and NPPB, SGLT1 and SGLT2 expression of hiPSC-derived cardiomyocytes. In addition, high glucose-treated hiPSC-derived cardiomyocytes exhibited reduced contractility regardless of the increased calcium transient capacity. Interestingly, application of empagliflozin before or after high glucose treatment effectively reduced the high glucose-induced cardiac abnormalities. Since application of empagliflozin did not significantly alter viability or glycolytic capacity of the hiPSC-derived cardiomyocytes, it is plausible that empagliflozin exerts its effects via the down-regulation of SGLT1, SGLT2 and GLUT1 expression. These observations provide supportive evidence that may help explain its unexpected benefit observed in the EMPA-REG trial.

The mechanism of the suppressive effect of rice albumin (RA) on postprandial hyperglycemia after glucose loading was investigated. In order to examine if small peptides derived from RA are responsible for prevention of postprandial hyperglycemia, RA was hydrolysed to indigestible high-molecular-weight peptides (HMP) and low-molecular-weight peptides (LMP) by trypsin, HMP and LMP being fractionated by gel-filtration chromatography. In oral glucose tolerance test (OGTT), both HMP and LMP suppressed the increase in blood glucose levels. In vitro diffusion test results showed that HMP adsorbed glucose and retarded its diffusion rate like dietary fibers. On the other hand, LMP suppressed the expression of sodium-dependent glucose transporter-1 (SGLT1) in STC-1 cells. Therefore, the suppressive effect of RA on postprandial hyperglycemia would be due to the dual actions of HMP and LMP. Our results demonstrated the potential use of RA as a functional food material to prevent diabetes.

Scope: Previous results suggested that the effects of Salvia fruticosa tea (SFT) drinking on glucose regulation might be at the intestinal level. Here we aim to characterize the effects of SFT treatment and of its main phenolic constituent – rosmarinic acid (RA) – on the levels and localization of the intestinal Na+/glucose cotransporter-1 (SGLT1), the facilitative glucose transporter 2 and glucagon-like peptide-1 (GLP-1). Methods and results: Two models of SGLT1 induction in rats were used: through diabetes induction with streptozotocin (STZ) and through dietary carbohydrate manipulation. Drinking water was replaced with SFT or RA and blood parameters, liver glycogen and the levels of different proteins in enterocytes quantified. Two weeks of SFT treatment stabilized fasting blood glucose levels in STZ-diabetic animals. The increase in SGLT1 localized to the enterocyte brush-border membrane (BBM) induced by STZ treatment was significantly abrogated by treatment with SFT, without significant changes in total cellular transporter protein levels. No effects were observed on glucose transporter 2, Na+/K+-ATPase or glucagon-like peptide-1 levels by SFT. Additionally, SFT and RA for 4 days significantly inhibited the carbohydrate-induced adaptive increase of SGLT1 in BBM. Conclusion: SFT and RA modulate the trafficking of SGLT1 to the BBM and may contribute to the control of plasma glucose., We thank NANTA, Fábrica de Moagem do Marco S.A., Portugal, for offering the Soybean meal 47.5 (LC diet). M. F. A. was supported by the Foundation for Science and Technology, Portugal, through the grant SFRH/BD/12527/2003. This work was supported by the Foundation for Science and Technology, Portugal, through the research grant POCI/AGR/62040/2004.